While animal studies with long acting exenatide (LAR exenatide) have failed to show evidence of tachyphylaxis (i.e., reduction in pharmacological response over time) [95], a recent trial in type 2 diabetic patients indicated that gastric emptying may be more strongly slowed by twice daily exenatide than once weekly LAR exenatide [96], suggesting that continuous GLP-1 exposure could result in a diminutesution of pharmacological response, potentially reflecting changes in receptor activation and/or changes in vagal function. This evidence concerns the gene GCG and type 2 diabetes mellitus.